Transition metal-catalyzed nonoxidative decarboxylation reactions

Aimin Liu, Hong Zhang

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Decarboxylases typically utilize an organic cofactor or a transition metal coupled with dioxygen to activate their substrates. The recent characterization of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) has revealed that this enzyme adopts a TIM-barrel (β/α) 8 fold and employs a mononuclear transition metal center to decarboxylate the substrate in an oxidant-independent fashion. Thus, ACMSD represents a type of decarboxylation reaction that has been so far uncharacterized in biological systems. Several close homologues of ACMSD were analyzed, including isoorotate decarboxylase (IDCase), 5-carboxyvanillic acid decarboxylase (5-CVD), γ-resorcylate decarboxylase (γ-RSD), and 4-oxalomesaconate hydratase (OMAH). These enzymes are involved in the catabolism of tryptophan and vanillate, the biodegradation of hydroxylbenzoates, and the thymidine salvage pathways in certain organisms. They possess the signature sequence motifs of the amidohydrolase superfamily and likely share the same structural and mechanistic characteristics as that of ACMSD. Analysis of the sequence conservation and evolutionary relationship of ACMSD-related proteins suggests an emerging ACMSD protein family that includes ACMSD and ACMSD-like decarboxylases and hydratases with diverse substrate specificities, many of which are poorly understood in regard to their functions and mechanisms. Progress in the biochemical and structural characterization of ACMSD not only sheds light on the active site of this protein family but also promises the elucidation of the detailed catalytic mechanism of these novel transition metal-dependent nonoxidative decarboxylation reactions.

Original languageEnglish (US)
Pages (from-to)10407-10411
Number of pages5
JournalBiochemistry
Volume45
Issue number35
DOIs
StatePublished - Sep 5 2006

ASJC Scopus subject areas

  • Biochemistry

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